Commentary about nanotech, science policy and communication, society, and the arts

Tag Archives: bioinformatics

Points to anyone who recognized the paraphrasing of the title for the well-loved, Canadian movie, “I heard the mermaids singing.” In this case, it’s all about protein folding and data sonification (from an Oct. 20, 2016 news item on phys.org),

Transforming data about the structure of proteins into melodies gives scientists a completely new way of analyzing the molecules that could reveal new insights into how they work – by listening to them. A new study published in the journal Heliyon shows how musical sounds can help scientists analyze data using their ears instead of their eyes.

The researchers, from the University of Tampere in Finland, Eastern Washington University in the US and the Francis Crick Institute in the UK, believe their technique could help scientists identify anomalies in proteins more easily.

“We are confident that people will eventually listen to data and draw important information from the experiences,” commented Dr. Jonathan Middleton, a composer and music scholar who is based at Eastern Washington University and in residence at the University of Tampere. “The ears might detect more than the eyes, and if the ears are doing some of the work, then the eyes will be free to look at other things.”

Proteins are molecules found in living things that have many different functions. Scientists usually study them visually and using data; with modern microscopy it is possible to directly see the structure of some proteins.

Using a technique called sonification, the researchers can now transform data about proteins into musical sounds, or melodies. They wanted to use this approach to ask three related questions: what can protein data sound like? Are there analytical benefits? And can we hear particular elements or anomalies in the data?

They found that a large proportion of people can recognize links between the melodies and more traditional visuals like models, graphs and tables; it seems hearing these visuals is easier than they expected. The melodies are also pleasant to listen to, encouraging scientists to listen to them more than once and therefore repeatedly analyze the proteins.

The sonifications are created using a combination of Dr. Middleton’s composing skills and algorithms, so that others can use a similar process with their own proteins. The multidisciplinary approach – combining bioinformatics and music informatics – provides a completely new perspective on a complex problem in biology.

“Protein fold assignment is a notoriously tricky area of research in molecular biology,” said Dr. Robert Bywater from the Francis Crick Institute. “One not only needs to identify the fold type but to look for clues as to its many functions. It is not a simple matter to unravel these overlapping messages. Music is seen as an aid towards achieving this unraveling.”

The researchers say their molecular melodies can be used almost immediately in teaching protein science, and after some practice, scientists will be able to use them to discriminate between different protein structures and spot irregularities like mutations.

Proteins are the first stop, but our knowledge of other molecules could also benefit from sonification; one day we may be able to listen to our genomes, and perhaps use this to understand the role of junk DNA [emphasis mine].

About 97% of our DNA (deoxyribonucleic acid) has been known for some decades as ‘junk DNA’. In roughly 2012, that was notion was challenged as Stephen S. Hall wrote in an Oct. 1, 2012 article (Hidden Treasures in Junk DNA; What was once known as junk DNA turns out to hold hidden treasures, says computational biologist Ewan Birney) for Scientific American.

Getting back to 2016, here’s a link to and a citation for ‘protein singing’,

Joanna Klein has written an Oct. 21, 2016 article for the New York Times providing a slightly different take on this research (Note: Links have been removed),

“It’s used for the concert hall. It’s used for sports. It’s used for worship. Why can’t we use it for our data?” said Jonathan Middleton, the composer at Eastern Washington University and the University of Tampere in Finland who worked with Dr. Bywater.

Proteins have been around for billions of years, but humans still haven’t come up with a good way to visualize them. Right now scientists can shoot a laser at a crystallized protein (which can distort its shape), measure the patterns it spits out and simulate what that protein looks like. These depictions are difficult to sift through and hard to remember.

“There’s no simple equation like e=mc2,” said Dr. Bywater. “You have to do a lot of spade work to predict a protein structure.”

…

Dr. Bywater had been interested in assigning sounds to proteins since the 1990s. After hearing a song Dr. Middleton had composed called “Redwood Symphony,” which opens with sounds derived from the tree’s DNA, he asked for his help.

Using a process called sonification (which is the same thing used to assign different ringtones to texts, emails or calls on your cellphone) the team took three proteins and turned their folding shapes — a coil, a turn and a strand — into musical melodies. Each shape was represented by a bunch of numbers, and those numbers were converted into a musical code. A combination of musical sounds represented each shape, resulting in a song of simple patterns that changed with the folds of the protein. Later they played those songs to a group of 38 people together with visuals of the proteins, and asked them to identify similarities and differences between them. The two were surprised that people didn’t really need the visuals to detect changes in the proteins.

…

Plus, I have more about data sonification in a Feb. 7, 2014 posting regarding a duet based on data from Voyager 1 & 2 spacecraft.

Finally, I hope my next Steep project will include sonification of data on gold nanoparticles. I will keep you posted on any developments.

A Jan. 6, 2015 news item on Nanowerk features a proposal by US scientists for a Unified Microbiome Initiative (UMI),

In October [2015], an interdisciplinary group of scientists proposed forming a Unified Microbiome Initiative (UMI) to explore the world of microorganisms that are central to life on Earth and yet largely remain a mystery.

An article in the journal ACS Nano (“Tools for the Microbiome: Nano and Beyond”) describes the tools scientists will need to understand how microbes interact with each other and with us.

Microbes live just about everywhere: in the oceans, in the soil, in the atmosphere, in forests and in and on our bodies. Research has demonstrated that their influence ranges widely and profoundly, from affecting human health to the climate. But scientists don’t have the necessary tools to characterize communities of microbes, called microbiomes, and how they function. Rob Knight, Jeff F. Miller, Paul S. Weiss and colleagues detail what these technological needs are.

The researchers are seeking the development of advanced tools in bioinformatics, high-resolution imaging, and the sequencing of microbial macromolecules and metabolites. They say that such technology would enable scientists to gain a deeper understanding of microbiomes. Armed with new knowledge, they could then tackle related medical and other challenges with greater agility than what is possible today.

I sped through very quickly and found a couple of references to ‘nano’,

Ocean Microbiomes and Nanobiomes

Life in the oceans is supported by a community of extremely small organisms that can be called a “nanobiome.” These nanoplankton particles, many of which measure less than 0.001× the volume of a white blood cell, harvest solar and chemical energy and channel essential elements into the food chain. A deep network of larger life forms (humans included) depends on these tiny microbes for its energy and chemical building blocks.

The importance of the oceanic nanobiome has only recently begun to be fully appreciated. Two dominant forms, Synechococcus and Prochlorococcus, were not discovered until the 1980s and 1990s.(32-34) Prochloroccus has now been demonstrated to be so abundant that it may account for as much as 10% of the world’s living organic carbon. The organism divides on a diel cycle while maintaining constant numbers, suggesting that about 5% of the world’s biomass flows through this species on a daily basis.(35-37)

Metagenomic studies show that many other less abundant life forms must exist but elude direct observation because they can neither be isolated nor grown in culture.

The small sizes of these organisms (and their genomes) indicate that they are highly specialized and optimized. Metagenome data indicate a large metabolic heterogeneity within the nanobiome. Rather than combining all life functions into a single organism, the nanobiome works as a network of specialists that can only exist as a community, therein explaining their resistance to being cultured. The detailed composition of the network is the result of interactions between the organisms themselves and the local physical and chemical environment. There is thus far little insight into how these networks are formed and how they maintain steady-state conditions in the turbulent natural ocean environment.

Rather than combining all life functions into a single organism, the nanobiome works as a network of specialists that can only exist as a community

The serendipitous discovery of Prochlorococcus happened by applying flow cytometry (developed as a medical technique for counting blood cells) to seawater.(34) With these medical instruments, the faint signals from nanoplankton can only be seen with great difficulty against noisy backgrounds. Currently, a small team is adapting flow cytometric technology to improve the capabilities for analyzing individual nanoplankton particles. The latest generation of flow cytometers enables researchers to count and to make quantitative observations of most of the small life forms (including some viruses) that comprise the nanobiome. To our knowledge, there are only two well-equipped mobile flow cytometry laboratories that are regularly taken to sea for real-time observations of the nanobiome. The laboratories include equipment for (meta)genome analysis and equipment to correlate the observations with the local physical parameters and (nutrient) chemistry in the ocean. Ultimately, integration of these measurements will be essential for understanding the complexity of the oceanic microbiome.

The ocean is tremendously undersampled. Ship time is costly and limited. Ultimately, inexpensive, automated, mobile biome observatories will require methods that integrate microbiome and nanobiome measurements, with (meta-) genomics analyses, with local geophysical and geochemical parameters.(38-42) To appreciate how the individual components of the ocean biome are related and work together, a more complete picture must be established.

The marine environment consists of stratified zones, each with a unique, characteristic biome.(43) The sunlit waters near the surface are mixed by wind action. Deeper waters may be mixed only occasionally by passing storms. The dark deepest layers are stabilized by temperature/salinity density gradients. Organic material from the photosynthetically active surface descends into the deep zone, where it decomposes into nutrients that are mixed with compounds that are released by volcanic and seismic action. These nutrients diffuse upward to replenish the depleted surface waters. The biome is stratified accordingly, sometimes with sudden transitions on small scales. Photo-autotrophs dominate near the surface. Chemo-heterotrophs populate the deep. The makeup of the microbial assemblages is dictated by the local nutrient and oxygen concentrations. The spatiotemporal interplay of these systems is highly relevant to such issues as the carbon budget of the planet but remains little understood.

And then, there was this,

Nanoscience and Nanotechnology Opportunities

The great advantage of nanoscience and nanotechnology in studying microbiomes is that the nanoscale is the scale of function in biology. It is this convergence of scales at which we can “see” and at which we can fabricate that heralds the contributions that can be made by developing new nanoscale analysis tools.(159-168) Microbiomes operate from the nanoscale up to much larger scales, even kilometers, so crossing these scales will pose significant challenges to the field, in terms of measurement, stimulation/response, informatics, and ultimately understanding.

Some progress has been made in creating model systems(143-145, 169-173) that can be used to develop tools and methods. In these cases, the tools can be brought to bear on more complex and real systems. Just as nanoscience began with the ability to image atoms and progressed to the ability to manipulate structures both directly and through guided interactions,(162, 163, 174-176) it has now become possible to control structure, materials, and chemical functionality from the submolecular to the centimeter scales simultaneously. Whereas substrates and surface functionalization have often been tailored to be resistant to bioadhesion, deliberate placement of chemical patterns can also be used for the growth and patterning of systems, such as biofilms, to be put into contact with nanoscale probes.(177-180) Such methods in combination with the tools of other fields (vide infra) will provide the means to probe and to understand microbiomes.

Key tools for the microbiome will need to be miniaturized and made parallel. These developments will leverage decades of work in nanotechnology in the areas of nanofabrication,(181) imaging systems,(182, 183) lab-on-a-chip systems,(184) control of biological interfaces,(185) and more. Commercialized and commoditized tools, such as smart phone cameras, can also be adapted for use (vide infra). By guiding the development and parallelization of these tools, increasingly complex microbiomes will be opened for study.(167)

Imaging and sensing, in general, have been enjoying a Renaissance over the past decades, and there are various powerful measurement techniques that are currently available, making the Microbiome Initiative timely and exciting from the broad perspective of advanced analysis techniques. Recent advances in various -omics technologies, electron microscopy, optical microscopy/nanoscopy and spectroscopy, cytometry, mass spectroscopy, atomic force microscopy, nuclear imaging, and other techniques, create unique opportunities for researchers to investigate a wide range of questions related to microbiome interactions, function, and diversity. We anticipate that some of these advanced imaging, spectroscopy, and sensing techniques, coupled with big data analytics, will be used to create multimodal and integrated smart systems that can shed light onto some of the most important needs in microbiome research, including (1) analyzing microbial interactions specifically and sensitively at the relevant spatial and temporal scales; (2) determining and analyzing the diversity covered by the microbial genome, transcriptome, proteome, and metabolome; (3) managing and manipulating microbiomes to probe their function, evaluating the impact of interventions and ultimately harnessing their activities; and (4) helping us identify and track microbial dark matter (referring to 99% of micro-organisms that cannot be cultured).

In this broad quest for creating next-generation imaging and sensing instrumentation to address the needs and challenges of microbiome-related research activities comprehensively, there are important issues that need to be considered, as discussed below.

David Bruggeman (Pasco Phronesis blog) has written up, as he so often does, a fascinating art/science piece in his May 28, 2015 post (Note: A link has been removed),

Opening next month [June 2015] at the Dilston Grove Gallery at GDP London is Music of the Spheres, an exhibition that uses bioinformatics to record music. Dr. Nick Goldman of the European Bioinformatics Institute has been working on new technologies for encoding large amounts of information into DNA. Collaborating with Charlotte Jarvis, the two have worked on installations of bubbles that would contain DNA encoded with music (the DNA is suspended in soap solution).

Music of the Spheres utilises new bioinformatics technology developed by Dr. Nick Goldman to encode a new musical recording by the Kreutzer Quartet into DNA.

The DNA has been suspended in soap solution and will be used by visual artist Charlotte Jarvis to create performances and installations filled with bubbles. The recording will fill the air, pop on visitors skin and literally bathe the audience in music.

Dr. Nick Goldman and Charlotte Jarvis have been working together for the past year to create a series of moving visual and musical experiences that explore the scope and future ubiquity of DNA technologies.

The Kreutzer Quartet’s new composition for string quartet loosely follows the traditional form of a concerto, in comprising of three musical movements. The second movement only exists in the form of a recording encoded into DNA.

For the exhibition the DNA will be suspended in soap solution and used to create silent installations filled with bubbles. The bubbles will be accompanied by a video projection showing the musicians playing in the server room of the European Bioinformatics Institute, Cambridge.

In response to the growing challenge of storing vast quantities of biological data generated by biomedical research Dr. Nick Goldman and the European Bioinformatics Institute have developed a method to encode huge amounts of information in DNA itself. Every day the huge quantities and speed of data pouring into servers gets larger. When research groups sequence DNA the file sizes are too large to be kept on local computers. It is this problem that was the motivation for Nick Goldman to develop his new technology. Their goal is a system that will safely store the equivalent of one million CDs in a gram of DNA for 10,000 years. Nick’s work was has been featured in The New York Times, The Guardian and on BBC News amongst other media outlets.

The Kreutzer Quartet will play the full-length composition live during the preview on 12 June [2015] timed with the setting of the sun through the large westerly windows. [emphasis mine] During the passage of the second movement the stage will fall silent, the music will be released into the auditorium in the form of bubbles. The performance will be accompanied by film projection and a discussion about the project.

The exhibit runs from June 12 – July 5, 2015. Hours and location can be found on the CGP website.

The Music of the Spheres DNA/music project was first mentioned here in a May 5, 2014 post about the launch of the book ‘Synthetic Aesthetics: Investigating Synthetic Biology’s Designs on Nature’. The launch featured a number of performances and events, scroll down abut 80% of the way for the then description of Music of the Spheres.

Unfortunately, there’s not much detail about the nanoparticle-based drug delivery of what I gather is a form of cannabis useful in the treatment of glaucoma in this April 16, 2015 news item on Azonano,

InMed Pharmaceuticals Inc., a clinical stage biopharmaceutical company that specializes in developing safer, more effective cannabinoid-based therapies, today announced that it has been awarded a grant to further develop the Company’s proprietary nanoparticle-based delivery system for their leading drug candidate CTI-085 for glaucoma.

The Mitacs grant was awarded to Dr. Maryam Kabiri, Ph.D., a researcher with extensive experience in developing nanoparticle-based delivery system. Dr. Kabiri will be working with Prof. Vikramaditya G. Yadav, whose research focuses on metabolic & enzyme engineering and customize novel biosynthetic enzymes that can convert biomass-derived feedstock into better fuels, pharmaceuticals and value-added chemicals. In conjunction with InMed, the Mitacs grant will be utilized to develop a novel delivery system for glaucoma therapy.

Dr. Sazzad Hossain, Chief Scientific Officer, states, “We are pleased to have met the Mitacs funding criteria for the advancement of our proprietary glaucoma delivery system. Not only does this bring us closer to our goals of initiating our Phase 1 trial, but it furthers our business development strategy of having a proprietary delivery system that can be licensed with existing drugs endangered by patent expiration. This “therapy extension” strategy used by drug makers can be a valuable asset to InMed upon successful completion of the program. Additionally, the incorporation of an existing medicine into a new drug delivery system can significantly improve its performance in terms of efficacy, safety, and improved patient compliance.”

About Mitacs
Mitacs is a national, private not-for-profit organization that develops the next generation of innovators with vital scientific and business skills through a suite of unique research and training programs, such as Mitacs-Accelerate, Elevate, Step, Enterprise and Globalink. In partnership with companies, government and universities, Mitacs is supporting a new economy using Canada’s most valuable resource – its people.

For more information on Mitacs, visit www.mitacs.ca.

About InMed
InMed is a clinical stage biopharmaceutical company that specializes in developing cannabis based therapies through the Research and Development into the extensive pharmacology of cannabinoids coupled with innovative drug delivery systems. InMeds’ proprietary platform technology, product pipeline and accelerated development pathway are the fundamental value drivers of the Company.

As is becoming increasingly common, there’s a major focus on business even from Dr. Sazzad Hossain, the company’s chief scientific officer who might be expected to comment on the science. Business used to be the purview of the chief executive officer, the chief financial officer, the chief operating officer, and/or the chief marketing officer.

I did manage to dig up a bit of information about InMed which was called Cannabis Technologies until fairly recently. Daniel Cossins in a Dec. 1, 2014 article for The Scientist describes the current ‘cannabis pharmaceutical’ scene. The dominant player on the scene is a UK-based company, GW but InMed merits a mention,

Leading scientists were consulted, including biotech entrepreneur Geoffrey Guy, who had previously shown interest in developing cannabis-based medicines. The government granted Guy’s company, GW Pharmaceuticals, a license to grow cannabis plants. Guy’s idea was to generate strains rich in particular cannabinoid compounds that act on the nervous system, then test the effects of various cannabinoid combinations on MS and chronic pain. “It was a case of patient experience guiding scientific exploration,” says Stephen Wright, director of research and development at GW.

In 2010, the company announced the UK launch of its first cannabinoid-based product: Sativex, an oral spray for the treatment of MS spasticity, became the world’s first prescription medicine made from cannabis extracts. Sativex is now approved for use by MS patients in 24 countries, including France, Germany, Italy, and Australia. GW has partnered with Bayer and Novartis to market the product. It has also signed up with the American branch of Japanese pharma company Otsuka to commercialize the drug in the U.S., where it is currently in Phase 3 clinical trials for treating MS spasticity and cancer pain. Earlier this year, GW’s share price surged when the US Food and Drug Administration (FDA) granted orphan status to its cannabis-derived antiseizure drug Epidiolex, meaning it will be fast-tracked through clinical trials.

The company’s success is blazing a trail. In recent years, a handful of North American companies have set out on a similar path toward producing cannabis-derived pharmaceuticals. At least one company is developing candidates based on synthetic cannabinoids — of which two are already on the market in the U.S. — while several others are extracting chemical cocktails from the plant. They’re all hoping to capitalize on the anticipated growth of the cannabis pharma space by taking advantage of mounting data on the plant’s therapeutic effects.

“Frankly, we looked at GW and saw that the shift toward pharmacological development of marijuana is already happening,” says Craig Schneider, president and CEO of InMed Pharmaceuticals (formerly Cannabis Technologies), a Vancouver-based biotech focused on pharmaceutical marijuana. “We see the likes of Otsuka, Novartis, and Eli Lilly diving into the space, and we want to be part of that.”

Cossins’ article goes on to discuss cannibinoids providing a tutorial of sorts on the topic. Meanwhile following on the business aspects of this story, Yahoo Finance hosts a June 25, 2014 article from Accesswire, which provides some insight into the company, which was still being called Cannabis Technologies, and its GW aspirations,

Cannabinoids are a diverse set of chemical compounds that act on cannabinoid receptors on cells that repress neurotransmitter release in the brain. While tetrahydrocannabinol (“THC”) and cannabidiol (“CBD”) are the two most popular cannabinoids, there are at least 85 different cannabinoids isolated from cannabis exhibiting various effects that could prove therapeutic.

GW Pharmaceuticals plc (GWPH), a biopharmaceutical company focused on discovering, developing, and commercializing novel therapeutics from its proprietary cannabinoid platform, has become the cannabinoid industry’s poster child with a ~$1.4 billion market capitalization and promising data from the clinic for the treatment of Dravet syndrome and Lennox-Gastaut syndrome.

In this article, we’ll take a look at another opportunity in the sector that many are calling the “junior GW” [InMed Pharma, formerly Cannabis Technologies], focused on leveraging its proprietary Cannabinoid Drug Design Platform to rapidly develop cannabinoid-based therapies.

…

Fully Integrated Platform Play

Cannabis Technologies Inc. (CSE:CAN) (CANLF) is a biopharmaceutical drug discovery and development company focused on cannabinoids that has been dubbed by many as the “Junior GW” in the space. By leveraging its proprietary Cannabinoid Drug Design Platform, management aims to identify new bioactive compounds within the marijuana plant that interact with certain genes.

According to Chief Science Officer Sazzad Hossain, the platform provides the bioinformatics tools necessary to isolate and identify chemical compounds in medical marijuana in months instead of years. The company plans to use the platform to isolate compounds targeting a specific disease and then outsource the early-stage research and trials to get to Phase I quickly and inexpensively.

The company’s initial focus is on the $12 billion ocular diseases market, including the $5.7 billion glaucoma market, where its CTI-085 is preparing to undergo Phase I clinical trials shortly after having completing preclinical trials. In addition to these areas, management also expressed interest in larger market places like pain and inflammation, as well as orphan diseases, cancers, and metabolic diseases.

Similar to GW Pharmaceuticals, the company also operates a breeding and cultivation division that’s responsible for creating its medicines in-house. The proprietary phyto-stock produced by the division sets the firm apart from some of its competitors that rely on third-parties to manufacture their treatments, since the fully-integrated operations are often both lower cost and greater quality.

…

They certainly have high business hopes for InMed Pharma. As for the science, the company has a Cannabinoid Science webpage on its site,

The majority of pharmaceutical and academic research & development being performed with cannabis revolves around the understanding of its active ingredients, the Cannabinoids

Currently there are between 80-100 cannabinoids that have been isolated from cannabis, that affect the body’s cannabinoid receptors and are responsible for unique pharmacological effects.

There are three general types of cannabinoids: herbal cannabinoids which occur uniquely in the cannabis; endogenous cannabinoids produced in the bodies of humans and animals and synthetic cannabinoids produced in the laboratory.

…

I was not able to find anything about the company’s nanoparticle-based delivery system on its website.

Alex Kawrykow and Gary Roumanis from McGill University (Montréal, Québec) have launched Phylo, a genetics game that anyone can play but is actually genetic research. From the article by Neal Ungerleider at the Fast Company website,

The new project, Phylo, was launched by a team at Montreal’s McGill University on November 29. Players are allowed to recognize and sort human genetic code that’s displayed in a Tetris-like format. Phylo, which runs in Flash, allows users to parse random genetic codes or to tackle DNA patterns related to real diseases. In a random game, a user found himself assigned to DNA portions linked to exudative vitreoretinopathy 4 and vesicoureteral reflux 2.

…

Players choose from a variety of categories such as digestive system diseases, heart diseases, brain diseases and cancer. All the DNA portions in the game are linked to different diseases. Once completed, they are analyzed and stored in a database; McGill intends to use players’ results in the game to optimize future genetic research.

This reminds me of Foldit (mentioned in my Aug. 6, 2010 posting) another multiplayer online biology-type game; that time the focus was protein folding. As Ungerleider notes in his article, gaming is being used in education, advertising, and media. I’ll add this, it’s also being used for military training.

I was interested to note that the McGill game was made possible by these agencies,

* Natural Sciences and Engineering Research Council of Canada
* McGill School of Computer Science
* McGill Centre for Bioinformatics
* McGill Computational Structural Biology Group

On a side note, there’s another biology-type game called Phylo, it’s a trading card game designed by David Ng, a professor at the University of British Columbia. From the Phylo, trade card game About page,

What is this phylo thing? (Some interesting but relatively specific FAQs here)

Well, it’s an online initiative aimed at creating a Pokemon card type resource but with real creatures on display in full “artistic” wonder. Not only that – but we plan to have the scientific community weigh in to determine the content on such cards, as well as folks who love gaming to try and design interesting ways to use the cards. Then to top it all off, members of the teacher community will participate to see whether these cards have educational merit. Best of all, the hope is that this will all occur in a non-commercial-open-access-open-source-because-basically-this-is-good-for-you-your-children-and-your-planet sort of way.

The Phylo, trading card game is in Beta (for those not familiar with the term beta, it means the game is still being tested, so there may be ‘bugs’).

It’s nice to be able to report on some innovative Canadian crowdsourcing science.